2680
COMMUNICATIONS TO THE EDITOR
Vol. 85
effect for the reaction is exceedingly small, indicating very little C-S bond-breaking a t the transition state.4 These effects are so strong that we must conclude that the proton positions in the transition states for these Benzh'itrile pinacol reactions are product-like, i . e . , have a larger H--0 Solvent Azine yield, 't yield, % than C-H stretching force constant. DO- in DzO is a Cyclohexane Benzal 85 82 at stronger base than HO- in Hz0 by a factor of cn. 1.(i Cyclohexane o-Chlorobenzal 88 84 Thus, even allowing for a substantial solvent Benzene p-Chlorobenzal 82 80 isotope effect (say 20%) superimposed upon the secondBenzene p-Methoxybenzal 82 i9 ary isotope effect due to the attacking base, we still Dioxane p - Sitrobenzal 95 93 conclude that the proton must be considerably deBenzene p-Dimethylaminobenzal 80 78 tached from the carbon atom in the transition state. a The yields are based on 1-5-g. experiments, repeated I t is very probable that the secondary isotope effect thrice, and averaged. The products were isolated in pure state k ~ / for k attack ~ of DO- vs. HO- must be considerably by distillation or crystallization and the yields were checked with larger for the ammonium compound than for the sulextraction procedures and gas chromatography. The last three fonium compound even after correction for possible entries of Table I required longer irradiation times to obtain the stated yields. T h e best procedure is to irradiate the solutions solvent isotope effects caused by the fact that the DOuntil the yellow golden color uf the azines disappears or becomes reaction is carried out in DzO while the HO- reaction is very faint. carried out in HzO. The solvent isotope effects should be weak and also should be similar for both compounds tization4 but an example of triplet or diradical hydrobecause in both cases a positively charged organic ion gen t r a n ~ f e r . ~The mechanism can be outlined as reacts with base. h. Coupled with the primary isotope effects for elimina(CsHs)zC=O r/- ( CsHs)zC=O* (1) tions under similar conditions, our results provide even ( C6H5)2C=0*+ CsHj-CH=S-K=CH-CsH. stronger evidence. For C6H6CD2CH2S+(CH3jzBra . C6H5-c=N--N=CH-c& + (CsH5)2C-oH (2) vs. the corresponding completely nondeuterated comC6Hj-c=N-K==CH-C& + (C.&&)?C=O pound k ~ ' k 1 1= 4.14 in HzO with HO-- a t 5.05 in 2CsHj-cN + (C6Hj)?C-OH (3) HzO a t 50°, 5.93 in HzO a t 30°, and 5.07 in ethanol with ethoxide a t 30'. The effect for the compound with 2( C B H ~ ) ~ C - O H +benzpinacol (4) trimethylamine as leaving group in place of dimethyl The synthetic usefulness of the reaction is somewhat sulfide is 2.98 in ethanol with ethoxide ion a t 50' and clouded because aldehydes are normally employed to 3.02 in 50% ethanol-water a t 50'. These relatively synthesize the azine derivatives. Synthesis of the small isotope effects indicate that the respective transiazines6 is, however, exceedingly simple and the yields tion states have either a considerably larger H-0 are quantitative. Possible extension of this reaction to than C-H stretching force constant or a considerably the aliphatic series is being investigated. larger C-H than H-0 stretching force constant. For Acknowledgment.-This work was supported by a equal C-H and H-0 stretching force constants, a grant (P-058) from the Robert A . iVelch Foundation. maximal isotope effect is expected8 (assuming that (4) G S. H a m m o n d , ? ? F T u r r o , a n d P A I,eermakers, J . P h y s . Chem 6 6 , effects due to bending vibrations are small relative to 1144 (1962) those due to stretching vibrations and 'or are nearly ( 5 ) See W M. Moore, G. S. H a m m o n d , and R . P Foss, J . A m . C h e m . Soc.. constant for transition states with different degrees of 83, 2789 (1961), a n d ref cited: S G Cohen, S. O r m a n , a n d D A 1-aiifer, proton transfer). For example, a large isotope effect, i b i d . , 84, 3905 (1962); S. G. Cohen and W V. Sherman, i b i d , 86, 1612 (1968) k~ ' k l , = 7.11 in ethanol with ethoxide a t SO', is ob(6) H H H a t t , "Organic Syntheses," Coll. Vol 11, John Wiley a n d Sons, served for C6H5CD2CH2Br,3 indicating the proton is Inc., N e w Y o r k , S . Y 1943, p 395 approximately equally tightly bound by C and 0 in the J O E E. HODCKINS DEPARTMENT O F CHEMISTRY transition state. JAMES A . KING TEXAS CHRISTIAN UNIVERSITY FORT WORTH,TEXAS The relative values of the secondary isotope effects RECEIVEDJ C N E 27, 1963 show that the proton is more tightly attached to the oxygen atom in the ammonium transition state than in the sulfonium transition state. Then the only way the Elimination Mechanisms. Position of Proton in E2 ammonium compound can have a smaller primary isoTransition States' tope effect than the sulfonium compound is if the proton is more strongly bonded to oxygen than to carbon in the Sir: ammonium transition state. This evidence is based \Ve have found that the isotope effects for DO- in only on the relative magnitudes of the secondary and D z 0 v s . HO- in HzO as attacking bases in the E2 elimination reactions of two /3-phenylethyl derivatives (4) U'. H . Saunders, Jr , a n d S . Aqperger, ibid , 79, 1612 (19.57) ~ 1.79 for C6H5CH2CH2N4(CH3j3Br(.5) Calculated from d a t a given b y C G. Swain and R F W Bader, a t 80' are k ~ ' , k = Teli,ahe,iro,t. 10, 197 (1960) I t is t h e square root of their equilibrium conBr- salts.* and 1.57 for C6H6CH2CHzS+(CH3)2 s t a n t for eq 9, i e , 1.79 a t 2 5 O , a n d , f r o m the t e m p e r a t u r e dependence of The effect for the sulfonium salt is complicated by A recent estimate of c n 1 2 s 3 probably too equilibria 7 and 8, 1 6 a t 80° exchange of D for H on the carbon atoms adjacent to the louy, is given b y A. J . Kresge a n d A. I-. Allred. J A m . Chem S o < , 86, 1341 (1963) This l o w value does n o t seem consistent with their value f o r t h e sulfur atom. Any isotope effect from this source relative acidities of D 3 0 + a n d t h e self-ionization constants of D20 and H s 0 sLould be small, however, because the sulfur isotope TABLE I" YIELD OF SUBSTITUTED KITRILES FROM THE CORRESPONDING AZINES
--+-
._
( I ) Supported in p a r t b y t h e United S t a t e s Atomic Energy Commission, t u which royalty-free right of reproduction is hereby granted Acknowledgm e n t is made t c r t h e donors of t h e Petroleum Research F u n d , administered b y t h e American Chemical Society, for partial support of this research ( 2 ) Our r a t e constant f o r H O - with t h e sulfonium salt agrees well with t h a t in t h e literature 2 R a t e c o n s t a n t i were measured by titration. for t h e a m m o n i u m compound, t h e amine was removed under reduced pressure before titration of each aliquot (:i) W H Saunders, Jr , a n d D H Edison, J A m C h e m S o c , 82, 138 (1960)
Using t h e two values of t h e isotope effect on t h e self-ionization of water. t h e D O - - H O - e f f e c t is either 1.79 or 2 27 a t 2.5' ( W F. K . Wynne-Jcmes. T r a n s F n v a d n y Soc , 3'2, I397 (1936); R UI. Kingerly and V. K 1.a !+fer. .I A m ('hem SM.. 63, 3256 (1911), it is not clear why t h e discrepancy exists) However, for reactions which appear t o proceed r,in a prior equilihrium which convert? hydroxide t o water, t h e kinetic isotope effects seem too small t c i be consistent with a value a s high a s 2.27 For example, t h e cyclization of ethylene chlorohydrin is faster with D O - in DzO by a factur of 1 ,54 rC. G Swain, A D Ketley, a n d R F W Bader, ;bid , 81, 2%53 (1959): P Ballinger a n d F A 1,ong. i b i d . , 81,2347 (1959)). 16) F H . m'estheimer. Chew Ret' , 61. 26.5 (1991) .
Sept. 5 , 1963
COMMUNICATIOXS TO THE EDITOR
primary isotope effects and is, therefore, separate from the evidence based on the absolute magnitudes of the secondary isotope effects. From these two pieces of evidence, we conclude that the proton is almost completely transferred to oxygen in the transition state for E2 elimination by HO- in HzO on C6H5CH2CH21J+(CH3)2. For the corresponding sulfonium ion, the proton is less completely transferred, and for the bromide, the proton is still less completely transferred. This work demonstrates how primary and secondary isotope effects in the same reaction can complement one another. The rates of elimination of 6-phenylethyl compounds substituted in the ring lead to good Hammett pu correlations. The chloride, bromide, iodide, tosylate, and dimethylsulfonium leaving groups all give p values between 2 and 3 with sodium ethoxide in ethanol a t 30°, these large values indicating considerable carbanion character in the transition state^.^ Although large p values could conceivably be due t o other factors than carbanion character, e.g., to the incipient double bond conjugated with the ring in the transition state, our results show that the proton is substantially transferred in these transition states. We plan to extend this method to other systems because it should help to explain the Hofmann-Saytzeff orientation effects which are currently ascribed to steric influences8 by some investigators and to electrical influences by other investigator^.^ 17) W. H . Saunders, J r , and R. A. Williams, J . A m . Chem. Soc., 79, 3712 fl957); W. H. Saunders, J r . , C. B Gibbons, and R . A . Williams, ibid., 80, 4099 (1958); C . H. D e P u y and D H . Fromsdorf, ibid., '79, 3710 (1957); C . H . D e P u y and C A. Bishop. ibid.,83, 2,532, 2535 (1960). T h e p value for trimethylammonium under t h e same conditions is even larger, 3.77 (W. H . Saunders, Jr , and D. G Bushman, unpublished). (8) H . C Brown. in " T h e Transition S t a t e , " Special Publication No. 16, T h e Chemical Society, London, 1962, p p 143-144. (9) D V. Banthrope, E . D . Hughes, a n d C. K . Ingold, J . Chem. Soc., 4054 (1960).
2681
clusively. The cyclic diesters were readily isolated in crystalline form; they were converted into the original triesters by diazomethane and were characterized also as cyclohexylammonium and piperidinium salts.
+
CH,OH
0,
,o
200
Iv 0.l';OH iCHjOH
Trimethyl phosphate and dimethyl p h o s p h ~ a c e t o i n ~ were not affected by water in benzene solution under comparable conditions. It seems possible that the formation of cyclic phosphodiesters from cyclic phosphotriesters, a t least in aprotic solvents, may proceed by way of an oxyphosphorane intermediate V. In other words, it may be possible under certain conditions to hydrate the phosphoryl group of a cyclic phosphate ester.
v
If an oxyphosphorane V is indeed an intermediate in DEPARTMEST OF CHEMISTRY LOUISJ. STEFFA USIVERSITYOF PENSSYLVANIA EDWARD R. THORNTONthe hydrolysis of a cyclic triester to a cyclic diester, the PHILADELPHIA 4, PESNSYLVANIA collapse of the oxyphosphorane must occur with preserRECEIVED J U X E 17, 1963 vation of the five-membered ring, since an open-chain
The Hydrolysis of Five-Membered Cyclic Phosphotriesters to Cyclic Phosphodiesters' Sir: The alkaline hydrolysis of methyl ethylene phosphate is much faster than t h a t of trimethyl phosphate and occurs with P-0 fission and ring The heat of saponification of methyl ethylene phosphate exceeds that of dimethyl 2-hydroxyethyl phosphate by about 5.5 kcal./'mole.2c Several hypotheses have been advanced to explain these kinetic and thermodynamic observation~.~, Recently, Covitz and Westheimer3 found that the hydrolysis of methyl ethylene phosphate in acid solution gave predominantly methyl 2-hydroxyethyl hydrogen phosphate, and, in addition, some ethylene hydrogen phosphate (from 5 to 30%). There was, therefore, some preservation of the five-membered ring. \Ve have observed that certain five-membered cyclic phosphotriesters (I, 111) react very rapidly with one mole equivalent of water in aprotic solvents a t 20°, yielding cyclic phosphodiesters I1 and IV almost ex(1) We gratefully acknowledge t h e support of t h e Cancer Institute of t h e National Institutes of Health (CY-4769), t h e S a t i o n a l Science Foundation ( G 19309). a n d t h e Petroleum Research F u n d of t h e American Chemical Society (286-A) ( 2 ) ( a ) P. Haake and F. H . Westheimer, J . A m . Chem Soc., 83, 1102 (1961). and references therein; (b) R . E. Wall, Thesis, Harvard University, 1960, (c) E T Kaiser, M. P a n a r , and F. H . Westheimer, J . A m . Chem Soc., 8 6 , 602 (1963) (3) F Covitz and F H Westheimer, i b i d . , 86, 1773 (1963).
diester should not cyclize under the experimental conditions. Some information on the mode of collapse of cyclic oxyphosphoranes analogous to V can be obtained from a study of the hydrolysis of the crystalline pentaalkoxyphosphorane VI in aprotic solvents, using water enriched with Ole. We had previously shown,5 using unlabeled water, that this hydrolysis is extremely fast and gives rise to the cyclic phosphotriester I. CH30
bCH3
VI O
h' 10
CHI
+
2 CH30H
The experiments with labeled water have shown that the oxygen atom of the water becomes attached to the phosphorus of the phosphate ester, presumably as a phosphoryl group, PO. Precisely how this happens remains a problem on the mechanism of substitution a t quintuply-connected phosphorus; however, the results suggest the participation of an oxyphosphorane VI1 in the hydrolysis of the pentaalkoxyphosphorane VI. Evidently, VI1 tends to collapse with preservation of the five-membered ring, since the product is a cyclic phosphate I. Therefore, the oxyphosphorane V, (4) F. Ramirez, B. Hansen, and P;.B. Desai, ibid , 84, 4888 ( 1 9 6 2 ) . (5) F. Ramirer, h-,B. Desai, and N R a m a n a t h a n , i b i d , 86, 1874 (1963)
